A common difficulty associated with surgical procedures is extensive bleeding or leaks of other bodily fluids and gases, resulting, for example, from incomplete tissue reattachment. Surgical adhesives can be used to help reattach tissues and to help seal tissue injuries, and thus to control the extent of undesired leaks. For example, tissue adhesives can be used as sealants to minimize blood loss, by applying them on injured blood vessels.
However, many currently available surgical adhesives and sealants still suffer from serious drawbacks.
Some of the synthetic adhesives used have low biocompatibility, low adherence to wet surfaces and potential toxicity, and others have low mechanical strength, tendency to swell and are costly.
Biological adhesives such as fibrin adhesives show poor mechanical tissue-bonding properties, their adherence to wet surfaces is limited, and they are potentially immunogenic, as they are based on proteins.
Another common complication associated with surgical procedures is postoperative adhesion, i.e. unwanted tissue growths occurring between layers of adjacent tissues or between tissues and internal organs. Adhesions are often induced by the healing process, and when present might cause numerous postsurgical complications, including patient's pain, functional obstruction, and sometimes difficult reoperation.
To solve these problems, physical barriers have been used to isolate the traumatized tissue from surrounding organs. Various natural and synthetic polymer films, membranes, and nonwoven fabrics have been developed as nonabsorbable or absorbable physical barrier materials. These barriers are reported to be effective in reducing postoperative adhesions, however they have limitations including difficulty in handling for their lack of flexibility, loose contact with applied tissue, and need for sutural fixation because of their sheet-like form.
Materials such as carbohydrates and in particular alginates may be formed into layers and films that may be useful as biocompatible substrates, for use as surgical devices. However, such compositions are not considered to have adhesive properties, and are commonly used externally as wound dressings or internally as adhesion-barriers.
For example, U.S. Pat. No. 6,638,917 to SCIMED LIFE SYSTEMS, INC. [US] describes devices for insertion into a body to reduce adhesion, which has an adhesion-barrier, the device including ionically cross-linked alginate.
Some of the devices according to U.S. Pat. No. 6,638,917 are described to additionally have strengthening fillers, which are added to alginate which is cross linked outside the body. Therefore, while augmenting the mechanical strength of the device. These devices require suturing, which might be damaging to the tissue.
PCT/GB1997/001244 to: ADVANCED MEDICAL SOLUTIONS [GB] relates to a hydrogel product that comprises coherent fibrous structure impregnated with an aqueous solution of a hydrogel precursor material, said fibres incorporating cations which are capable of cross-linking said precursor material to form a fibre reinforced hydrogel as the hydrogel product.
Similarly, EP1607412 to First Water Ltd. [GB] describes a hydrogel/fibre composite that includes fibres of a fibrous material impregnated with a precursor solution comprising at least one polymerisable, and optionally also cross linkable, monomer such that at least partial swelling of the fibres takes place; and polymerizing, and optionally also cross-linking, the at least one monomer after impregnation the cross-linking not initiated solely by cation release from the fibres of the fibrous material.
Both PCT/GB1997/001244 and EP1607412 describe wound dressings in the form of a hydrogel, which is non-adhesive, and intended for external use to support wound healing.
U.S. Pat. No. 5,804,213 to LECTEC CORPORATION [US] relates to a prepackaged wound dressing including dry particulate solids that are dispersed in a liquid and then applied to a wound, the solids forming a gel. The actual dispersion is performed before application.
JP 2145505 to KOKEN KK [JP] describes a removable sheet pack for application to skin that includes a support, e.g. nonwoven fabric, crosslinkable gel (alginic acid and a water soluble polymer such as polyvinyl pyrrolidone, and cross linking agent, e.g. calcium chloride.
Therefore, the references cited above refer to carbohydrate compositions that include a solid support and have cross-linked layers that were created ex-situ, require employing means such as suturing to attach the compositions in-situ, or are used externally on skin.
Some water-soluble carbohydrate compositions are described to have poor adhesive properties.
For example, WO07/066,837 to LG HOUSEHOLD & HEALTH CARE LTD. [KR] describes an adhered teeth whitening film prepared in-situ, from water-soluble agents that include for example alginate and a calcium ion-source, which form together a water-insoluble film on the surface of teeth in the oral cavity through in situ gelling. However, in order to improve the adherence to teeth, an additional compound is included with one of the agents. Indeed, it is stated that a disadvantage of conventional alginate systems is poor adhesion.
Similarly, U.S. Pat. No. 6,193,994 to SAMYANG CORPORATION [KR] describes a dental composition prepared in-situ, which is stated to enable a drug to remain in a periodontal pocket for a prolonged time. The composition is said to be prepared by making a mixture of microspheres containing a drug and a water-soluble polymer such as a polysaccharide, making the mixture into the form of film or strip or/and coating the film or strip with a cation aqueous solution such as calcium or barium.
However, the longevity of the composition is due to complexation of the polymer with the cation decreasing the solubility of the composition in water and slowing the rate of swelling of the composition.
Such compositions, while perhaps suitable for uses such as dental treatment, lack mechanical strength and adherence, typically required in compositions for uses such as placement within a patient during a surgical procedure for adhesion to a tissue.
One object of the present invention is to provide simple, non-toxic, strong, strongly adhesive and economical tissue adhesives, suitable for example for sustaining internal surgical incision closure.
Another object of the present invention is to provide a physical barrier that adheres, preferably strongly and effectively, to a tissue, thereby reducing or obviating the need for sutural fixation, while still providing desired isolation from nearby organs and tissues.
For example, in those surgeries where a tissue adhesive is used as a sealant to minimize leaks, it would be beneficial if the said sealant could also function as a tissue adhesion barrier.
It is another object of the present invention to provide methods of application of the adhesive in the site that requires tissue repair, tissue sealing or other treatments. The materials and methods of application may involve the use of additional materials other than the glue.